Department of Neurosurgery, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan.
Department of Clinical Laboratory Sciences, School of Health Sciences, Fukushima Medical University, Fukushima 960-8516, Japan.
Int J Mol Sci. 2022 Apr 16;23(8):4414. doi: 10.3390/ijms23084414.
Gliomas are among the most common tumors of the central nervous system and include highly malignant subtypes, such as glioblastoma, which are associated with poor prognosis. Effective treatments are therefore urgently needed. Despite the recent advances in neuroimaging technologies, differentiating gliomas from other brain diseases such as multiple sclerosis remains challenging in some patients, and often requires invasive brain biopsy. Protein tyrosine phosphatase receptor type Z (PTPRZ) is a heavily glycosylated membrane protein that is highly expressed in the central nervous system. Several reports analyzing mouse tumor models suggest that PTPRZ may have potential as a therapeutic target for gliomas. A soluble cleaved form of PTPRZ (sPTPRZ) in the cerebrospinal fluid is markedly upregulated in glioma patients, making it another promising diagnostic biomarker. Intriguingly, PTPRZ is also involved in the process of remyelination in multiple sclerosis. Indeed, lowered PTPRZ glycosylation by deletion of the glycosyltransferase gene leads to reduced astrogliosis and enhanced remyelination in mouse models of demyelination. Here, we review the expression, molecular structure, and biological roles of PTPRZ. We also discuss glioma and demyelinating diseases, as well as the pathological role of PTPRZ and its application as a diagnostic marker and therapeutic target.
神经胶质瘤是中枢神经系统最常见的肿瘤之一，包括高度恶性的亚型，如胶质母细胞瘤，其预后较差。因此，迫切需要有效的治疗方法。尽管神经影像学技术最近有了进步，但在某些患者中，区分神经胶质瘤与其他脑部疾病（如多发性硬化症）仍然具有挑战性，通常需要进行有创性的脑活检。蛋白酪氨酸磷酸酯酶受体 Z 型（PTPRZ）是一种高度糖基化的膜蛋白，在中枢神经系统中高度表达。几项分析小鼠肿瘤模型的报告表明，PTPRZ 可能是神经胶质瘤的潜在治疗靶点。脑脊液中可溶性裂解形式的 PTPRZ（sPTPRZ）在神经胶质瘤患者中明显上调，使其成为另一种有前途的诊断生物标志物。有趣的是，PTPRZ 还参与多发性硬化症的髓鞘再生过程。事实上，通过删除糖基转移酶基因降低 PTPRZ 的糖基化，会导致脱髓鞘小鼠模型中的星形胶质细胞增生减少和髓鞘再生增强。在这里，我们回顾了 PTPRZ 的表达、分子结构和生物学作用。我们还讨论了神经胶质瘤和脱髓鞘疾病，以及 PTPRZ 的病理作用及其作为诊断标志物和治疗靶点的应用。
